Previous studies documented the frequent occurrence of severe, progressive malnutrition in AIDS. The long-term goal of our studies is to provide an understanding of the pathogenesis of malnutrition in AIDS, a scientific rationale for nutritional therapy, and realistic expectations for the results of such therapy. The specific aims of this proposal are to define the metabolic mechanisms underlying the alterations in body composition that occur as a result of the acquired immune deficiency syndrome, their association with active HIV infection, and their relationship to altered release of cytokines. The centerpiece of these studies will be precise measurements of body composition which will allow precise determination of depletion or repletion. Two approaches will be taken to study the problem. A cohort of asymptomatic, HIV-seropositive men will be studied and followed longitudinally. Estimations are that a subgroup will undergo clinical progression, and that the changes will include body mass depletion. Studies of energy utilization and substrate flux will be performed to determine what type of alterations occur and at what point in the disease. Correlations will be made with serum levels of cytokines. The other approach will be to study malnourished AIDS patients who are undergoing nutritional or antiviral therapy. Recent studies have demonstrated the feasibility of providing nutritional support to these patients and have shown body mass repletion as a result of effective antiviral therapy. Nutritional studies will be performed during the period of repletion and the results correlated with serum levels of cytokines. In later years, the nutritional and metabolic effects of modulating cytokine release will be studied. The ability to mitigate the nutritional consequences of chronic infections in AIDS may be important in reducing the morbidity of such complications.